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Title: Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-κB pathway

Abstract

Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the effect of Celecoxib, a COX-2 inhibitor on two molecular breast cancer subtypes—MDA-MB-231 and SK-BR-3. Firstly, MDA-MB-231 and SK-BR-3 cells were treated with various concentration of Celecoxib for 24 and 48 h. Celecoxib-inhibition of NF-κB (p52 and p65) transcriptional activity and effect of Caspase 3 pathway were examined by western blotting. COX-2 mRNA was assessed by RT-PCR. Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazoliumbromide (MTT) assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. We found that Celecoxib inhibited the proliferation of the MDA-MB-231 cell line in a dose-time dependent manner versus SK-BR-3 in a dose dependent manner only (p < 0.05). Celecoxib induced apoptosis of the MDA-MB-231 and SK-BR-3 cell lines in a dose-time dependent manner (p < 0.05) with more mean apoptotic cells in MDA-MB-231 than SK-BR-3. Significant cell-cycle arrest at the G1 phase in the MDA-MB-231 versus G2 phase in SK-BR-3 cell lines. NF-κB (p52 and p65) and COX-2 expressions were downregulated in a dose dependent manner, while Caspase 3 expression was upregulated in both cell lines. In this present study, our data indicated Celecoxib might affect each breast cancer subtype independently. Therefore,more » when using Celecoxib in treatment of breast cancer, it is imperative to consider the subtype of breast cancer on a molecular level. - Highlights: • We assumed and proved the correlation of levels of caspase-3, NF-κB (p52, p65) expression in the two types of breast cancer cells (i.e. MDA-MB-231 and SKBR3), and to determine whether exposure to different concentrations of Celecoxib has an impact in expression of these apoptotic and anti-apoptotic pathways respectively. • The difference in effect of Celecoxib was investigated in the two molecular subtypes of breast cancer cells i.e. MDA-MB-231 (ER–, PR–, HER2–) and SKBR3 (ER–, PR–, HER2+ Ki67 high) with regard to proliferation and cell cycle analysis. • In our study, we demonstrated that when using Celecoxib in treatment of breast cancer, it is imperative to consider the subtype of breast cancer on a molecular level.« less

Authors:
 [1];  [2]; ;  [1];  [1];  [1]
  1. Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, 227 Yanta West Road, Xi'an, Shaanxi Province 710061 (China)
  2. Department of Radiology, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Xi'an, Shaanxi Province 710068 (China)
Publication Date:
OSTI Identifier:
22719056
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 490; Journal Issue: 3; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; CONCENTRATION RATIO; DOSES; INHIBITION; MAMMARY GLANDS; MESSENGER-RNA; NEOPLASMS; POLYMERASE CHAIN REACTION; THERAPY; TIME DEPENDENCE

Citation Formats

Wang, Guanying, Li, Jian, Zhang, Lingxiao, Huang, Shangke, Zhao, Xinhan, and Zhao, Xiaoai. Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-κB pathway. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.06.148.
Wang, Guanying, Li, Jian, Zhang, Lingxiao, Huang, Shangke, Zhao, Xinhan, & Zhao, Xiaoai. Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-κB pathway. United States. doi:10.1016/J.BBRC.2017.06.148.
Wang, Guanying, Li, Jian, Zhang, Lingxiao, Huang, Shangke, Zhao, Xinhan, and Zhao, Xiaoai. Sat . "Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-κB pathway". United States. doi:10.1016/J.BBRC.2017.06.148.
@article{osti_22719056,
title = {Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-κB pathway},
author = {Wang, Guanying and Li, Jian and Zhang, Lingxiao and Huang, Shangke and Zhao, Xinhan and Zhao, Xiaoai},
abstractNote = {Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the effect of Celecoxib, a COX-2 inhibitor on two molecular breast cancer subtypes—MDA-MB-231 and SK-BR-3. Firstly, MDA-MB-231 and SK-BR-3 cells were treated with various concentration of Celecoxib for 24 and 48 h. Celecoxib-inhibition of NF-κB (p52 and p65) transcriptional activity and effect of Caspase 3 pathway were examined by western blotting. COX-2 mRNA was assessed by RT-PCR. Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazoliumbromide (MTT) assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. We found that Celecoxib inhibited the proliferation of the MDA-MB-231 cell line in a dose-time dependent manner versus SK-BR-3 in a dose dependent manner only (p < 0.05). Celecoxib induced apoptosis of the MDA-MB-231 and SK-BR-3 cell lines in a dose-time dependent manner (p < 0.05) with more mean apoptotic cells in MDA-MB-231 than SK-BR-3. Significant cell-cycle arrest at the G1 phase in the MDA-MB-231 versus G2 phase in SK-BR-3 cell lines. NF-κB (p52 and p65) and COX-2 expressions were downregulated in a dose dependent manner, while Caspase 3 expression was upregulated in both cell lines. In this present study, our data indicated Celecoxib might affect each breast cancer subtype independently. Therefore, when using Celecoxib in treatment of breast cancer, it is imperative to consider the subtype of breast cancer on a molecular level. - Highlights: • We assumed and proved the correlation of levels of caspase-3, NF-κB (p52, p65) expression in the two types of breast cancer cells (i.e. MDA-MB-231 and SKBR3), and to determine whether exposure to different concentrations of Celecoxib has an impact in expression of these apoptotic and anti-apoptotic pathways respectively. • The difference in effect of Celecoxib was investigated in the two molecular subtypes of breast cancer cells i.e. MDA-MB-231 (ER–, PR–, HER2–) and SKBR3 (ER–, PR–, HER2+ Ki67 high) with regard to proliferation and cell cycle analysis. • In our study, we demonstrated that when using Celecoxib in treatment of breast cancer, it is imperative to consider the subtype of breast cancer on a molecular level.},
doi = {10.1016/J.BBRC.2017.06.148},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 490,
place = {United States},
year = {2017},
month = {8}
}